Alterations in social reward and body perception brain circuits in anorexia nervosa: a functional and structural neuroimaging investigation

Abstract

Anorexia nervosa (AN) is a severe disorder, accepted to be of a multifactorial etiology. Although there is evidence for alterations in neural networks contributing to the onset, development and maintenance of AN, the knowledge of alterations of brain circuits is very limited. To this purpose, we investigated in three MRI experiments (two published, one in review) putative alterations in brain systems in a group of 20 female outpatients with AN, restrictive subtype, compared to a group at 20 female healthy controls. The first study aimed, in an exploratory manner, to find alterations in white matter tracts microstructure; important in the context of brain systems and the major shaping of white matter in adolescence, a vulnerable period for AN development (Study 1). To evaluate alterations in brain function, we aimed at targeting either alterations in a system known to present abnormal responses in AN: the reward system, but in a social context (Study 2), or brain alterations associated with a core symptom of the disorder: own-body processing alterations (Study 3). In Study 1, we looked at differences in quantitative scalar measures in white matter tracts, derived from diffusion tensor imaging techniques (DTI). There were two clusters of significant between-group differences, at the superior longitudinal fasciculus (SLF)-parietal parts and at the fimbria-fornix (FFo). The pattern of alterations was different, possibly corresponding to myelinisation deficits in SLF and more complex pathophysiological processes overlapped at the FFo. The location of differences suggested a link with body distortion or alterations in the reward associated with food. In Study 2, we evaluated between-group brain differences in the response to receiving either social acceptance (reward) or rejection (punishment). Patients showed differences in the dorsomedial prefrontal cortex during acceptance and in visual areas during rejection, interpreted as a motivational biased response for social relationships: low engagement in positive feedbacks and hyperattention to negative ones. Interaction and correlation analyses between brain activation and sensitivity to reward/punishment or the severity of the disorder suggested an aberrant modulation of reward areas -frontal opercula/anterior insula, ventral striatum- involved in responses to social acceptance and rejection, respectively. In Study 3, we evaluated alterations in body processing during the visualization of video-recorded own- and another’s body. The interest was in the self-evaluative component of body processing; to this purpose, our analyses were focused to brain activity differences within the default mode network (DMN). In regions with between-group differences, we additionally evaluated functional connectivity differences with other areas of the DMN during either at rest or the task. Medial parietal areas, at the dorsal posterior cingulated cortex (dPCC) and at the Precuneus, showed differences due either to an hyperresponse of patients to the own-body evaluation (dPCC) or a lack of a differential response in patients to the processing of another’s body (Precuneus). There was an additional increased dPCC to anterior cingulate cortex during own processing but decreased with angular gyrus during resting-state in patients. These results were interpreted as increased ruminative state during own-body processing in AN, possibly associated with body distortion, as well as a putative more tonic, task-unrelated alterations of posterior DMN regions. Moreover, there was an increased precuneus to mid temporal cortex

functional connectivity during the other’s processing in patients; alterations to the other’s body were possibly related to alterations in social cognition processes. The three studies support alterations in two systems, a prefronto-parietal circuit -possibly associated with alterations in body processing- and in a reward/motivational system. The integration of these results in current research lines resulted in the presentation of a new theoretical frame for AN, linking self-body image, relation to others, and alterations in social interaction and reward responses.

La anorexia nerviosa es un trastorno grave y de etiología multifactorial. Actualmente se sabe que existen alteraciones en diversos circuitos cerebrales, que, a pesar de la reciente emergencia de técnicas como la deep brain stimulation (DBS) que pretenden modularlos, no conocemos suficiente. En la presente tesis se evaluaron alteraciones neuroestructurales y neurofuncionales en un grupo de 20 pacientes mujeres con anorexia nerviosa (AN), subtipo restrictivo, mediante técnicas de resonancia magnética (RM).

En el primer estudio evaluamos diferencias en la microestructura de los tractos de sustancia blanca. Se encontraron alteraciones posiblemente relacionadas con distintas alteraciones de la microsestrutura en el fascículo longitudinal superior y en el fórnix. En el segundo estudio, y en relación con la creciente importancia de las alteraciones del sistema del refuerzo en AN, se evaluó la respuesta cerebral durante una situación experimental de aceptación o rechazo social. Se hallaron diferencias en la respuesta del área dorsomedial del córtex prefrontal y de áreas visuales. La actividad de estructuras del sistema del refuerzo como la ínsula y el núcleo estriado ventral se hallaron vinculadas a rasgos de personalidad y a la severidad del trastorno, influyendo en diferencias en la respuesta cerebral. En el tercer estudio, se pretendió evaluar las alteraciones de la percepción de la imagen corporal asociadas a un componente autoevaluativo. Se hallaron alteraciones en áreas de la red neuronal por defecto (RND), así como en su conectividad funcional durante la tarea y durante el estado de reposo. Las alteraciones se presentaron durante la autopercepción corporal, pero también en la percepción del cuerpo de otra persona. De forma integrada, los resultados de los tres estudios (dos publicados y uno en revisión) sugirieron la presencia de alteraciones funcionales y estructurales, en AN, en un sistema fronto-parietal, posiblemente asociado con la distorsión de la imagen corporal, también en áreas vinculadas a la motivación en un contexto social, así como en áreas del sistema de refuerzo. Los resultados, integrados en el marco de las líneas de investigación actuales, sirvieron para la presentación de un nuevo marco teórico que vincula la autopercepción corporal, interacción social y respuestas al refuerzo.